In assessing the treatment landscape for PIK3CA-mutated breast cancer, researchers observed that patients with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative breast cancer have poorer outcomes and more resistance to chemotherapy than those with PIK3CA-mutated triple-negative breast cancer (TNBC; Ann Oncol. 2020;31:377-386).
Although PI3K inhibitors have been shown to improve outcomes in patients with PIK3CA-mutated, HR-positive, HER2-negative metastatic breast cancer, it is still undetermined how to integrate this new drug family in the treatment landscape, according to Fernanda Mosele, MD, Gustave Roussy, Villejuif, France, and co-investigators.
Dr Mosele et al examined the mutational profiles of 649 patients with metastatic breast cancer from the SAFIR02 trial for outcome analysis. PIK3CA mutations were assessed with next-generation sequencing (NGS) followed by whole-exome sequencing, and NGS and digital PCR were used to evaluate the prognostic value of PIK3CA mutations during chemotherapy.
PIK3CA mutations were present in 28% of HR-positive, HER2-negative tumors and 10% of TNBCs, and overall survival (OS) outcomes were worse for patients with PIK3CA-mutated, HR-positive, HER2-negative metastatic breast cancer versus PIK3CA wild-type.
In addition, the researchers observed that PIK3CA-mutated, HR-positive, HER2-negative metastatic breast cancers had enhanced MAP3K1 mutations.
Among patients with metastatic TNBC, the median OS was 24 months for patients with PIK3CA mutations versus 14 months for those with PIK3CA wild-type. When looking at the distribution of PIK3CA mutation in metastatic TNBC, 36% of patients with HR-positive primary tumors had PIK3CA mutations compared with 6% of patients without HR expression.
Notably, the level of residual PIK3CA mutations in plasma after cycles of chemotherapy was associated with poor OS.
Thus, Dr Mosele and colleagues concluded that patients with PIK3CA-mutated, HR-positive, HER2-negative metastatic breast cancer have poor outcomes and more resistance to chemotherapy than those with PIK3CA-mutated TNBC.
“This could be explained by an enrichment of PIK3CA mutations in luminal BC [breast cancer] which lost HR expression in the metastatic setting,” they wrote.—Kaitlyn Manasterski
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